This is a renewal application for 1R01 DA21146-01, a Bioengineering Research Partnership (BRP) to develop real-time prospective motion correction (PMC) for MRI. Magnetic resonance imaging (MRI) is a powerful technique for assessing the structure, function, and physiology of the human brain in vivo. MRI affords high spatial and temporal resolution, is non-invasive and repeatable, and may be performed in children. However, motion continues to be a substantial problem in many MR studies, especially those performed in children, infants, or subjects who are agitated or confused due to anxiety, drug use or sickness, resulting in data with motion artifacts that may prevent accurate diagnoses or assessments. Prospective motion correction can dramatically attenuate motion artifacts by dynamically tracking the motion of the head/brain during a scan, and continuously correcting acquisitions such that they are locked relative to the moving brain. In the initial project period, we made substantial progress in developing optical-based motion tracking and correction for MRI. While the initial prototype system performs well for relatively small and slow movements, the system may fail to sufficiently attenuate motion artifacts during clinically relevant motions (larger amplitudes and higher speed). The proposed competitive renewal will focus on resolving these issues, with the following specific Aims. (1) Improve robustness of motion correction with optical tracking. (2) Develop techniques for motion correction at higher velocities (up to 100mm/s and /s), and implement these methods for a set of clinically relevant sequences. (3) Develop reconstruction techniques for data acquired during head motion. (4) Demonstrate clinical efficacy and utility of the motion correction methods developed. The work will be performed by an experienced team of investigators with a track record of collaboration, using modern 3T and 7T scanners. Implementing these innovations will increase the availability of adaptive motion correction technologies for the clinical arena, and promise improved and more robust MR scans in children and patients who have difficulty holding still, both in research and clinical settings.